1. Prepared for Pitt Street Health
Effient® (prasugrel) for the reduction of atherothrombotic events in ACS in patients with UA, NSTEMI and STEMI managed with PCI
Therapeutic Review
Prepared for Pitt Street Health
Kimberly Garrison
Jaewoo Lee
Aleksandra Stojkoska
Brittany Thompson

2. Outline Acute Coronary Syndrome
Epidemiology
Demographics and Cost
Diagnosis
Treatment
Thienopyridine Pharmacokinetics/Pharmacodynamics
CYP2C19 Interactions
Non-responders
Proton Pump Inhibitor use
JUMBO-TIMI 26
TRITON-TIMI 38
PRINCIPLE-TIMI 44
Economic Considerations
Recommendation
Like I said before I will be starting off describing Acute Coronary Syndrome – It’s Epidemiology, demographics and costs, diagnosis, treatment as well as pharmacokinetics and Pharmacodynamics
I will then hand it off to Jason who will be discussing the therapeutic non response and CYP2C119 interactions as well as the JUMBO Timi trial
Brittany will then present the triton timi and principle timi trials and their findings.
Kim will then finish of the presentation with Economic Considerations and the final recommendation

3. Acute Coronary Syndrome Epidemiology
Leading cause of death in The United States
25% of deaths
445,687 people died from coronary heart disease in 2005
17,600,000 people alive with coronary heart disease
316.4 billion dollars in costs in 2010
So why is Pitt Street Evaluating a drug for ACS?
This is very important because Coronary heart disease is the current leading cause of death in the United States. It accounts for 25% of deaths
Almost 500,000 people died in 2005 from coronary heart disease
And 17.6 million people in the world are currently living with heart disease
These disease alone costs around 300 billion dollars in 2010 – A large cost burden in the Untied
CDC: Heart Disease Facts. [Internet]. Atlanta: Center for Disease Control and Prevention. America's Heart Disease Burden; 2010 Dec 21 [Cited 2011 Jan 15]; Available from:

4. Acute Coronary Syndrome Pitt Street Health Demographics
 Plan Enrollment: ,650,000
 Incidence
Patients
<65 years
Patients years
≥75 years
Total
Diagnosis with ACS
0.51%
5,755
3,033
4,688
13,476
Undergoing a PCI
30.8%
2,283
973
897
4,153
Cost per day associated with ACS events
Repeat PCI
$20,060
Stroke
$12,143
Angina
$4,794 MI
$15,086
CABG
$46,002
Other Vascular Intervention
$18,280
Other Cardiac Conditions
$9,683
If we look at specifically at Pitt Street Health we can see these cost first hand.
Out of the 2.65 million people in the plan we calculated an incident rate of 0.5% in the plan. This accounts for around members.
Out of those members about 30 percent of them will undergo a PCI. About 4000 members with that.
So if we look at the costs per event per day of various events that occur with ACS we can see that there is a big cost burden to the plan.
One way to decrease this burden is the decrease the amount of hospitalizations but using a more effective drug therapy.
Effient® (prasugrel) Dossier. Eli Lilly and Daiichi-Sankyo. Prepared using AMCP format for formulary submissions, version 2.1.

5. Acute Coronary Syndrome Diagnosis
When patient arrive at the hospital with symptoms of ACS there are 3 different possible diagnosis: An STEMI, NSTEMI or Unstable Angina.
To determine this an ECG is given and interpreted and different cardiac markers such as creatine kinase, troponins and CK-MB isoenzymes.
If the ECG shows an ST elevation and is positive for cardiac markers it is referred to as STEMI
IF the ECG does not show ST elevation it can still be an MI because it shows increase levels in cardiac markers. This is known as a non-STEMI
Lastly, If a patient is negative for cardiac markers the diagnosis is Unstable Angina.
The Diagnosis is very important to the types of treatment the patient will receive.
Alpert et al. J Am Coll Cardiol 36 (3): 959–69

6. Acute Coronary Syndrome Treatment
Upon hospital arrival:
MONA
Morphine, oxygen, nitroglycerine, aspirin
Beta blockers
Only if an increase in heart rate is present
Upon discharge:
Statin
Beta-blocker
Aspirin
Ace Inhibitor/ARB
Thienopyridine
After the ASC event is diagnosed the treatment follows a basic pattern
When a patient first arrives in the hospital Morphine, oxygen, nitroglycerine and aspirin are given
Beta Blockers may also be given if the patient has a increased heart rate.
When patients are discharged they are given Statin Therapy, a beta blocker, a thienopyridine ( 95% of the will be Plavix), Aspirin and an Ice Inhibitor or and ARB when ace inhibitors cannot be given.
- Five new drugs could be overwhelming for patients and This is a great opportunity for pharmacists to step in and make sure all the therapies are correct and the patient’s are counseled and understand how to correctly take the drugs.
Blais D. Acute coronary syndromes. Presentation given at: The Ohio State University chapter of Academy of Managed Care Pharmacy. General body meeting Nov 9th; Columbus,OH.

7. Platelet Inhibitors Thienopyridines
Clopidogrel
Prasugrel
Ticagolor
Loading Dose mg
60mg
180mg
Maintenance Dose
75 mg daily
10 mg daily
90 mg twice daily
Route
Oral
Binding to P2Y12
Irreversible
Reversible
Prodrug
Yes No
Hepatic Metabolism
CYP C219
CYP 3A, 2B6,2C19
None
Platelet Inhibition
40%
~70%
95%
Onset
2 hours
minutes
The medications that we are specifically looking at are the thienopyridines.
These 3 medications: Clopidogrel, prasugrel and tricagolor are all FDA approved oral drugs.
I want to draw your attention to the bottom 3 rows when comparing Clopidogrel and Prasugrel
When you compare metabolism you can see that Clopidogrel and Prasugrel are metabolized by different enzymes.
This is important because it will affect platelet levels – And Jason will explain this in detail next.
Also when Prasugrel is compared the Clopidogrel – The platelet inhibition is higher and the onset is much shorter.
DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically.

8. Platelet Inhibitors Mechanism of Action
Lastly, I want to show the different mechanisms of actions and why Prasugrel stands out.
The three drugs structures are shown at the top of the figure and the bottom shows the path the drugs take to the P2Y12 receptor.
Tricagolor is shown at the top and orally active drug and is absorbed and does not go through any biotransformations. It then binds reversibly to the PY12 receptor then inhibiting their activation and decreasing platelet aggregation
Prasugrel is a prodrug and is not orally active. It is oxidized by a hepatic enzyme CYP and is converted to its active metabolite. It then binds irreversibly to the receptor – decreasing aggregation
Clopidogrel like Prasugrel is a Prodrug and is converted to its active metabolite. But the activation of Clopidiogrel is a two step CYP process for activation
Schomig a. N Engl J Med. 361:

9. CYP2C19 Interactions Therapeutic Non-response
A large contributing factor to the FDA wanting to find an alternative therapeutic treatment for ACS is the emergence of clopidogrel non-responders. Clopidogrel, once absorbed in the intestines, is then converted to its active thiol metabolite via a two-step reaction. As is shown in the figure, this is done by multiple CYP450 enzymes; however, the largest player and the one we are most concerned with non-response is CYP2C Approximately 25% of caucasions, 30% of African-Americans and 50% of Asians possess at least one variant allele and this, according to theory, puts them at an increased risk of platelet aggregation and recurrent ischemic events. While the evidence of non-response is quite solid, many questions are yet to be answered. This includes, most importantly, whether or not this interactions leads to an increased risk of recurrent ischemic events and morbidity/mortality.
Bonello et al. J Am Coll Cardiol. 2010;56:919-33

10. CYP2C19 Interactions Therapeutic Non-response
There are many studies available that observe the decrease in platelet aggregability in patients with a loss of function allele; however, none of them have enough power or the proper procedure to determine if these effects result in an increase in recurrent ischemic events. There are very few randomized-controlled trials that focus on this interaction; therefore, we are left with multiple meta-analysis looking prospectively on the situation. One of which to note with appropriate power is the CURE trial. These graphs show a kaplan-meier curve looking at event-free survival among patients with ACS. As shown, there is a non-significant difference in the occurrence of a first or second occurrence of a primary outcome. In light of these results, we have come to the conclusion that when determining which therapy is more appropriate for patients, a risk-benefit analysis is necessary. In low to medium risk patients, the use of clopidogrel may be acceptable because a lower platelet inhibition level may be all that is required to see effect. If it is known that the patient has a loss-of-function allele, this would be taken into account as another risk factor for recurrent ischemic events. If, however, the patient is considered high risk (ie. is diabetic or has a stent), prasugrel may be more appropriate since higher levels of platelet inhibition are necessary.
Primary Outcome Composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke
Pare et al. N Engl J Med Oct 28;363(18):

11. CYP2C19 Interactions Proton Pump Inhibitors
The concomitant use of proton pump inhibitors (PPIs) with antiplatelet agents has raised some controversy in recent years. The primary concern is the possible competitive inhibition by PPIs of the cytochrome P450 isoenzyme CYP2C19, which is responsible for metabolic activation of clopidogrel. Genetic polymorphisms of the CYP2C19 allele have been associated with an increased risk of adverse effects for patients treated with clopidogrel, thereby supporting the concept that diminished CYP2C19 activity can have a detrimental effect on outcomes. PPIs are thought to be converted by CYP2C19 as well, which reduces bioavailability of the enzyme for antiplatelet metabolism. The resulting effect would be reduced antiplatelet activity and the emergence of clopidogrel resistance in patients. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency currently warns physicians to re-evaluate the need for treatment with a PPI in patients taking clopidogrel and discouraging their combined use without a compelling indication. However, in a recent study regarding this issue, it was concluded that no significant association remained between the use of a PPI and risk of the primary endpoint, both for clopidogrel and prasugrel. The Kaplan-Meier graph shown indicates the rate of the primary endpoint (CV death, MI or stroke) throughout long-term follow-up (> 1 year) for both antiplatelet agents. For patients randomly assigned to clopidogrel, the rates were 11.8% for with PPI and 12.12% without, whereas for prasugrel they were 10.2% and 9.7%, respectively. After adjustment for potential confounders and the propensity to be treated with a PPI, there was no correlation between PPI use and risk of primary endpoints.
Clopidogrel is converted to its active metabolite via CYP enzymes, particulary CYP2C19
PPI’s, shown as omeprazole, are inactivated via the same CYP450 enzymes that activate clopidogrel
Concomitant use of clopidogrel with PPI’s theoretically reduces clopidogrel effectiveness which leads to worse outcomes
Madanick et al. Cleve Clin J Med. 2011 Jan;78(1):39-49.

12. CYP2C19 Interactions Proton Pump Inhibitors
The Kaplan-Meier graph shown indicates the rate of the primary endpoint (CV death, MI or stroke) throughout long-term follow-up (> 1 year) for both antiplatelet agents. For patients randomly assigned to clopidogrel, the rates were 11.8% for with PPI and 12.12% without, whereas for prasugrel they were 10.2% and 9.7%, respectively. After adjustment for potential confounders and the propensity to be treated with a PPI, there was no correlation between PPI use and risk of primary endpoints.
The following bar graph shows the proportion of non-responders and mean inhibition of platelet aggregation for PPI use with clopidogrel and prasugrel. 24 hours after a 600 mg loading dose of clopidogrel, the proportion of patients with thienopyridine hypo-responsiveness was more than two-fold higher for patients on a PPI than not. Moreover, after 15-days of follow-up, the proportion of patients with thienopyridine hypo-responsiveness to clopidogrel 150 mg a day was more than six-fold higher for patients on a PPI than not. On the other hand, very few patients had an inadequate response of any sort to prasugrel after 24 hours or 15 days of follow-up, regardless of whether PPIs were used.
Long-term follow-up and rate of primary endpoint (right); Proportion of non-responsders 6h (A) and 15 days (B) after clopidogrel or prasugrel stratified by the use of a PPI in PRINCIPLE-TIMI 44 (left)
O’Donoghue et al. Lancet Sep 1; 374:

13. JUMBO-TIMI 26 Study Design
Phase 2, multicenter, randomized, parallel-group, ITT, double-blind, active comparator-controlled trial
The first major trial we will discuss concerning prasugrel is a phase-2, dose-ranging safety trial comparing prasugrel with clopidogrel in patients undergoin PCI. As noted, this trial was multicenter, randomized, parallel-group, ITT, double-blind, with an active-comparator-control. The illustration shown described the study protocol which included 900 patients randomized to low dose (40mg LD followed by 7.5mg Daily), intermediate dose (60mg LD followed by 10mg Daily), or high dose (60mg LD followed by 15mg Daily) prasugrel or the standard dose of clopidogrel (300mg LD followed by 75mg Daily). All subjects received Aspirin EC 325mg daily for the duration of therapy. Primary endpoints for this trial include non CABG-related significant hemorrhage at 30 days, and MACE which includes death, MI, stroke, recurrent ischemia, CTVT.
Wiviott et al. Circulation Jun 20;111:

14. JUMBO-TIMI 26 Outcomes A B C D E F
The graphs shown on this slide give an overall view of the results obtained from the JUMBO trial. Graph A depicts the results of significant Non-CABG related bleeding and, as can be seen, there is a non-significant difference between clopidogrel and prasugrel, regardless of the dose. Graph B depicts the same results for TIMI Major Non-CABG bleeding. When looking at MACE over 30 days, there was a lower incidence in the overall prasugrel group; however, this was also nonsignificant compared to clopidogrel. Graph D does show a significant reduction in MI for the overall prasugrel group; however, when looking at the different doses of prasugrel, it is apparent the highest dose of prasugrel contributed to most of this significance. This dose is commonly not used because of the increased risk of adverse events. Graphs E and F also depict the increased efficacy of prasugrel versus clopidogrel. While this study was not powered to determine efficacy, it does provide the foundation for a large phase 3 clinical trial. Strength of this trial include a large sample size with 80% power in order to detect significant differences in non-CABG associated bleeding, it was a multicenter trial, had a small withdrawal rate, and a strong trial design. Limitations include 77% of subjects male, no statistical power to detect clinically meaningful differences in efficacy endpoints, reduced power for primary safety endpoint because bleeding rates were low, short study period, one clopidogrel arm, and funding from Eli Lilly.
Wiviott et al. Circulation Jun 20;111:

15. TRITON-TIMI 38 Study Design
TRITON-TIMI 38 is a phase 3, randomized, double-blind, double dummy, parallel-group with active comparator, ITT, multicenter trial. They enrolled 13,608 patients with ACS with a planned PCI and we assigned in two strata to either the prasugrel or clopidogrel dosing regimen. The two strata identified patients with either moderate to high risk UA/NSTEMI or STEMI. The LD was administered anytime between randomization and 1 hours after leaving the cath lab, then after PCI patients were given a MD of either prasugrel or clopidogrel for a total of 6-15 months. Patients were also required to be on Aspirin at mg daily.
Wibiott et al. Amer Heart Jour Oct;152(4):

16. TRITON-TIMI 38 Efficacy Outcomes
Efficacy Endpoints:
Primary:
Death from CV causes, non-fatal MI or non-fatal stroke
Secondary:
Stent thrombosis, rehospitalization
The graphs on this table show an analysis of the major efficacy endpoints of TRITON-TIMI 38: MI, Stent thrombosis and uTVR or urgent target vessel revascularization. The results are shown for the LD up to 3 days up through the entire trial period of approximately 15 months. As you can see, the reduction in the hazard ratio for MI (19%), stent thrombosis (51%) and uTVR (34%)was significant in favor of prasugrel. This trend of significant reduction in HR in favor or prasugrel also extends out through the maintenance dose phase to an even larger extent (MI -31%, stent thrombosis-55% and uTVR-35%).
Antman et al. JACC;51(21):

17. TRITON-TIMI 38 Safety Outcomes and Net Clinical Benefit
Stent thrombosis, rehospitalization, and TIMI major non-CABG bleed
Study Strengths:
Sample size adequate for 90% power, length of study, randomized, double-blinded
Study Limitations
Funding from Eli Lilly, did not use highest possible dose of clopidogrel, mostly white males
Safety outcomes for TRITON-TIMI 38 are shown and include stent thrombosis, rehospitalization and TIMI major non-CABG bleeding. A graph of the results for bleeding is shown on top and displays the bleeding rate through the first 3 days was numerically greater for prasugrel but without statistical significance. From 3 days through the end of the trial period; however, the rate of bleeding did reach a significantly higher level for prasugrel compared to clopidogrel. It was observed that there are specific groups of patients, those who had a previous stroke of TIA, those older than 75 years of age and patients weighing less than 60kg, that had higher rates of bleeding. It appears prasugrel causes significant harm in patients with a history of cerebrovascular events; therefore, the FDA issued a black box warning alerting health care professionals of the incresed risk in such patients populations. When these 3 groups of patients are taken out of the equation, prasugrel has greater efficacy (HR=0.74 p<0.0001) with no significant difference in the rate of major bleeding (HR=1.24, p=0.17). The graph on the lower portion of the slide shows the net clinical benefit of prasugrel vs. clopidogrel. This significantly favors prasugrel for the first 3 days and through the end of the study period with a reduction in the HR of 15% and 13% respecitvely. When taking the patients with history of a cerebrovascular event out of the equation, the net clinical benefit is substantially more favorable for prasugrel compared to clopidogrel.
Antman et al. JACC;51(21):

18. TRITON-TIMI 38 Special Populations - Diabetics
Of the 1300 some patients enrolled in TRITON-TIMI 38, 3146 had a preexisting history of diabetes including 776 receiving insulin. These graphs show the different efficacy and safety outcomes and net clinical benefits observed for patients with or without diabetes on either prasugrel or clopidogrel. There is a significant increase in the primary endpoint for diabetics vs. non-diabetics (14.6% vs. 9.9%). Furthermore, in subjects with DM, a 30% reduction in the primary endpoint was observed with prasugrel. This trend continues for MI as well. For TIMI major bleeding, there was little difference between diabetics and non-diabetics; however, patients who have DM have no significant difference in the rates of TIMI major bleeding. These observations prove that platelet aggregation plays a large part in diabetic complications and supports the use of more intesive platelet inhibitors, as it can be seen that the net clinical benefit of prasugrel is much greater in patients with diabetes than non-diabetics. Furthermore, as can be shown in the graph on the lower left, diabetic patients on insulin have an even greater benefit from prasugrel.
Wiviott et al. Circulation Aug 31;118:

19. TRITON-TIMI 38 Special Populations – Stent Placements
The graph to the left shows both early (0-30 days) and late (30 days on) thrombosis
At 0-30 days, stent thrombosis was reduced by 59% for prasugrel vs. clopidogrel (p<0.0001)
At 30 days on, stent thrombosis was reduced by 40% for prasugrel vs. clopidogrel (p=0.03)
Along with diabetes, stent-related ischemic events are probably largely related to platelet activation and aggregation; therefore, it is our theory that a higher level of platelet inhibition with prasugrel will give better outcomes than with lower platelet inhibitors such as clopidogrel. Of the 13,608 patients randomized in TRITON-TIMI 38, 12,844 patients received any kind of stent. There was a 19% reduction in the primary endpoint recorded with prasugrel in all of the patients receiving a stent compared to no stent. The effect seemed to be more pronounced in patients receiving bare-metal stents as opposed to drug-eluting stents. Overall, stent thrombosis was significantly reduced by prasugrel (58%). These results prove that stent thrombosis is largely related to platelet aggregation, and patients will likely benefit from a higher and more consistent level of platelet inhibition that is provided by prasugrel.
The table to the right shows the effect of prasugrel versus clopiogrel in key subgroups
The most significant treatment subgroup favoring prasugrel was in patients with a previous MI (p=0.047)
Wiviott et al. Lancet Apr 19;371:

20. PRINCIPLE-TIMI 44 Study Design
A major downside of the TRITON-TIMI was that it only looked at intermediate dose clopidogrel, whereas prescribers have recently been prescribing higher doses up to 150mg daily. This issue is addressed in the PRINCIPLE-TIMI 44 trial, which is a randomized, double-blind, multicenter, double-dummy, active comparator-controlled, 2-phase crossover study patients were randomized to receive either 600mg of clopidogrel or 60 mg of prasugrel in the LD phase. After PCI patients were to continue on the same drug at a maintenance dose of 150 mg clopidogrel or 10 mg of prasugrel for 14 days. After this 14 day period, patients crossed-over to taking the other maintenance dose medication for the remaining 14 days. Endpoints of the study include P: LD phase IPA 20 μmol/L at 6 hours. MD phase IPA 20μmol/L after 14+/- 2 days S: MPA of 20μmol/L ADP and mean VerifyNow.
Wiviott et al. Circulation Dec 3;116:

21. PRINCIPLE-TIMI 44 Loading Dose Phase
For the LD phse, the primary efficacy endpoint for IPA with 20 micromol/L ADP at 6 hours was significantly greater after preasugrel compred with clopidogrel. Furthermore, patients treated with prasugrel had mot consistent levels of platelet inhibition. These results were observed after 30 minutes of administration and was maintained for hours and fewer prasugrel subjects met the criteria for hyporesponsiveness. The antiplatelet effect of prasugrel was also greater, as can be seen in the two graphs above. The IPA for prasugrel was significantly (p<0.0001) higher than clopidogrel as well as the VASP PRI.
Primary efficacy endpoint significantly greater after prasugrel vs. clopidogrel (p<0.0001)
Patients treated with prasugrel had more rapid onset of inhibition observed at 30 minutes
Wiviott et al. Circulation Dec 3;116:

22. PRINCIPLE-TIMI 44 Maintenance Dose Phase
This slide shows the maintenance dose phase results starting at the day 15 evaluation and through the day 29 evaluation. The primary efficacy endpoint of IPA was significantly greater in subjects receiving prasugrel 10mg compared with clopidogrel 150mg both before and after the crossover occurred. These results were observed through both the IPA measurements as well as the VASP PRI. Furthermore, no TIMI major bleeds were observed in either treatment arm. These results suggest that even if a 150mg dose of clopidogrel is used in the future by physicians, there would still be a greater inhibition of platelet function with prasugrel 10mg.
Primary efficacy endpoint significantly greater for prasugrel vs. clopidogrel (p<0.0001)
Patients treated with prasugrel were observed to have more consistent levels of inhibition and few hyporesponsive episodes
Wiviott et al. Circulation Dec 3;116:

23. Economic Considerations Budget Impact Model
Model was designed to estimate the total annual costs for treating a population with either prasugrel or clopidogrel
Patients with no history of transient ischemic attack that are to undergo treatment with a thienopyridine
Patients took the thienopyridine for up to 15 months after PCI
Model assumes a 100% compliance rate of clopidogrel and prasugrel
Lacks consideration of other thienopyridine agents
Does not take into account other medications required to prevent an additional ACS event from occurring
Model results included a favorable incremental cost effectiveness ratio (ICER) over clopidogrel
Overall cost-benefit analysis conducted found treatment with prasugrel to decrease overall costs due to lower rate of rehospitalization involving PCI
Prasugrel is the economically dominant treatment strategy
Effient® (prasugrel) Dossier. Eli Lilly and Daiichi-Sankyo. Prepared using AMCP format for formulary submissions, version 2.1.

24. Economic Considerations Cost of Thienopyridine per year
Prasugrel
Clopidogrel
Year 1
$307,638
$4,954,940
Year 2
$1,154,511
$9,977,162
Year 3
$2,115,008
$7,055,834
Year 4
$2,402,058
$3,029,085
Year 5
$1,951,077
$3,192,024
At year 2 generic clopidogrel is introduced to the market
Number of eligible for treatment with a thienopyridine:
Percent of patients taking prasugrel / Percent of patients taking clopidogrel:
Year 1: 5 / Year 2: 10/ Year 3: 12/88
Year 4: 13/ Year 5: 15/85
. The Congress of the United States: Congressional Budget Office. July 1998: 1-70.
Hong SH et al.JMCP. 2005;11(9):

25. Economic Considerations Cost-Benefit Analysis
Prasugrel
Year 1
Year 2
Year 3
Year 4
Year 5
Total Cost/year
$270,523
$1,099,534
$1,918,375
$2,074,988
$657,125
PMPM
$0.09
$0.26
$0.37
$0.32
$0.20
PTMPM
$1,583
$1,508
$1,436
$1,368
$1,303
Clopidogrel
Year 1
Year 2
Year 3
Year 4
Year 5
Total Cost/year
$5,285,669
$9,829,033
$9,449,897
$4,290,514
$3,793,547
PMPM
$1.99
$3.71
$3.57
$1.62
$1.43
PTMPM
$1,658
$1,579
$1,620
$1,678
$1,360
Effient® (prasugrel) Dossier. Eli Lilly and Daiichi-Sankyo. Prepared using AMCP format for formulary submissions, version 2.1.

26. Economic Considerations Cost-Benefit Analysis
Direct Medical Savings
PMPM
PTMPM
Year 1
$5,015,147
$1.89
$1,621
Year 2
$9,037,202
$3.41
$1,461
Year 3
$8,312,709
$3.14
$1,344
Year 4
$3,271,909
$1.23
$1,074
Year 5
$3,136,422
$1.18
$1,035
Effient® (prasugrel) Dossier. Eli Lilly and Daiichi-Sankyo. Prepared using AMCP format for formulary submissions, version 2.1.

27. Recommendation for Pitt Street Health Formulary
Movement of prasugrel from non-preferred brand to preferred brand
Requires a prior authorization
Approved dose
Prasugrel 10 milligrams daily
Age Restrictions
Not approved for patients >75 yoa
Ineligible for treatment
Patients <60kg, prior TIA or CVA or CABG scheduled in next 7 days
Recommended follow-up
Two weeks, 1 month, then every 3 months thereafter
Recommended length of therapy
Left to the discretion of the health-care team
Be sure to refer them to the PA form in the handout

28. Recommendation Flow-chart for Decision Making
ACS patient
STEMI UA
First event?
NSTEMI Y N
Diabetic or previous stent?
TIMI
TIMI N Y
0-4 5+ 5+
Be sure to note that an extended version of this is available in both the monograph and the handout.
0-2
3-4
High
Intermediate
High
Intermediate
Low
Intermediate
High
High Risk: prasugrel
Intermediate Risk: prasugrel or clopidogrel
Low Risk: clopidogrel

29. Recommendation Role of Health-Care Practitioners
Physician/Cardiologist
Identifying patients as high, intermediate or low risk
Prescribing the appropriate dose of chosen thienopyridine
Monitoring of safety/efficacy of agent chosen
Clinical Pharmacist
Assisting the physician in identifying high, intermediate or low risk patients and determining the appropriate dose
Follow up with patient to assess safety/efficacy
Appropriately educating patient on proper use of thienopyridine
Community Pharmacist
Dispensing correct product from pharmacy
Medication therapy management and drug-utilization review of all medications the patient is currently taken

30. Prepared for Pitt Street Health
Effient® (prasugrel) for the reduction of atherothrombotic events in ACS in patients with UA, NSTEMI and STEMI managed with PCI
Therapeutic Review
Prepared for Pitt Street Health
Kimberly Garrison
Jaewoo Lee
Aleksandra Stojkoska
Brittany Thompson